International A Level Biology / Gene expression and genetics
Gene mutations: substitution, insertion, deletion
Edexcel International A Level Biology (YBI11), chapter 6: Gene expression and genetics, specification point 2.14. Free lesson.
Read the revision notes · International A Level Biology past papers
A gene mutation is a change in the base sequence of DNA, often caused by an error during DNA replication. The type of mutation affects how mRNA and proteins are made, which can change an organism’s phenotype or have no observable effect.
How a replication error becomes a mutation
Before a cell divides, DNA polymerase copies DNA by joining free nucleotides along each template strand. It is very accurate, but errors can still happen. Most are repaired. If an error remains, it is copied during the next replication and becomes part of the DNA sequence. A substitution is one base swapped for another. An insertion is an extra base added. A deletion is a base missed out.
What substitutions do to a codon
A codon is a group of three bases in mRNA that codes for an amino acid or a stop signal. The effect of a substitution depends on how the changed codon is read. The example is from the β-globin gene, which codes for part of haemoglobin. Original: GAG codes for glutamic acid (Glu). Silent: GAA still codes for glutamic acid, so the polypeptide is unchanged. This is possible because the genetic code is degenerate: most amino acids have more than one codon. Missense: GUG codes for valine instead. This substitution causes sickle cell anaemia. Nonsense: UAG is a stop codon, so the…
Why insertions and deletions can have a larger effect
mRNA is read in groups of three bases from the start codon, AUG, with no gaps. Adding or losing one or two bases shifts the reading frame, changing the grouping into codons. This usually changes every codon after the mutation. Original: AUG CAU GGC UUU AAC codes for Met His Gly Phe Asn. Insertion: AUG ACA UGG CUU UAA codes for Met Thr Trp Leu, then stop. Deletion: AUG AUG GCU UUA AC… codes for Met Met Ala Leu… Adding or losing three bases keeps the reading frame, because the sequence still has complete groups of three.
How a changed base can change phenotype
To explain the effect of a mutation, follow the chain from the DNA to the observable characteristic, or phenotype. A changed DNA sequence produces different mRNA codons, which may change the amino acid sequence, called the primary structure. Different R groups can form hydrogen bonds, ionic bonds and disulfide bridges in different places, changing the protein’s three-dimensional shape. A changed shape can affect the protein’s function. For example, an active site may no longer be complementary to its substrate. In sickle cell anaemia, haemoglobin forms long fibres at low oxygen, making…
Possible outcomes and accurate mutation names
Mutations can have different outcomes depending on their effects. Many have no observable effect because they are silent, occur in non-coding DNA, or do not change the protein’s shape. A mutation can cause a genetic disorder if a protein the body needs stops working. Examples include sickle cell anaemia and cystic fibrosis. A mutation in a gene controlling cell division can cause cancer. Cells may divide uncontrollably and form a tumour. Use the names substitution, insertion and deletion. A frameshift describes the effect of some insertions and deletions, not the mutation’s name.